Zhang Fei, Bian Yuhao, Huang Lei, Fan Wenbin
Department of Cardiothoracic Surgery, Nanshan People's Hospital, Shenzhen, Guangdong 518052, P.R. China.
Graduate School, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China.
Exp Ther Med. 2017 Nov;14(5):5170-5176. doi: 10.3892/etm.2017.5129. Epub 2017 Sep 19.
Structural and electrical remodeling within the atrium mediate the pathogenesis of atrial fibrillation (AF). Two key genes that sever a role in this remodeling are connexin 40 (Cx40) and potassium voltage-gated channel subfamily A member 5 (KCNA5), respectively. Electrical remodeling is considered to induce structural remodeling during AF. In the present study, the left atrial appendage section and atrial myocytes of patients with AF were evaluated. It was observed that Cx40 and KCNA5 mRNA (P<0.05) and protein (P<0.01) expression was significantly downregulated in AF compared with rheumatic heart disease. In addition, a positive correlation between the mRNA expression Cx40 and KCNA5 was observed in the atrial myocytes of patients with AF (P<0.05; r=0.42). The association between Cx40 and KCNA5 expression was subsequently investigated in primary cultured atrial myocytes using siRNA transfection. In atrial myocytes, downregulation of Cx40 inhibited the expression of KCNA5. Similarly, silencing of KCNA5 suppressed the expression of Cx40. These results indicate that synergistic regulation may occur between Cx40 and KCNA5 expression. Furthermore, the combined effects of electrical and structural remodeling in the atrial myocytes of patients with AF may contribute to the pathogenesis of AF.
心房内的结构和电重构介导了心房颤动（AF）的发病机制。在这种重构中起作用的两个关键基因分别是连接蛋白40（Cx40）和钾电压门控通道亚家族A成员5（KCNA5）。电重构被认为在房颤期间诱导结构重构。在本研究中，对房颤患者的左心耳切片和心房肌细胞进行了评估。结果观察到，与风湿性心脏病相比，房颤患者的Cx40和KCNA5 mRNA（P<0.05）及蛋白（P<0.01）表达显著下调。此外，在房颤患者的心房肌细胞中观察到Cx40和KCNA5的mRNA表达呈正相关（P<0.05；r=0.42）。随后，使用小干扰RNA（siRNA）转染在原代培养的心房肌细胞中研究了Cx40和KCNA5表达之间的关联。在心房肌细胞中，Cx40的下调抑制了KCNA5的表达。同样，KCNA5的沉默也抑制了Cx40的表达。这些结果表明，Cx40和KCNA5的表达之间可能存在协同调节。此外，房颤患者心房肌细胞中电重构和结构重构的联合作用可能促成了房颤的发病机制。
